Sagar Khare
@sagarkhare.bsky.social
Professor, Chemistry and Chemical Biology, Rutgers University. Interested in protein design, enzymes, molecular modeling, biophysics, AI/ML for bioX.
Here for science, society and lack of toxicity
Here for science, society and lack of toxicity
So, how does the chaperone HtrA1 do it? Well, it uses cool tricks: it uses two (important) places to bind not one, it not just binds but also cuts its target, and it binds to various species (seeds, monomers) along the aggregation pathway. See how we figured it out! (4/n)
December 3, 2024 at 10:13 AM
So, how does the chaperone HtrA1 do it? Well, it uses cool tricks: it uses two (important) places to bind not one, it not just binds but also cuts its target, and it binds to various species (seeds, monomers) along the aggregation pathway. See how we figured it out! (4/n)
In the classical inhibition paradigm, a protein is inhibited by (think antibodies) by binding tightly at one site. This is quite challenging to do if you have, literally, a very moving target in the form of a disordered protein. Moreover, aggregation pathways involve species with >1 chains (3/n)
December 3, 2024 at 10:13 AM
In the classical inhibition paradigm, a protein is inhibited by (think antibodies) by binding tightly at one site. This is quite challenging to do if you have, literally, a very moving target in the form of a disordered protein. Moreover, aggregation pathways involve species with >1 chains (3/n)
With this broader motivation and in collaboration with Jean Baum's group, we brought to bear a number of computational and experimental biophysical tools (including cool Atomic Force Microscopy in Liquids!) to figure out how HtrA1 inhibits the aggregation and prion-like spread of a-synuclein. (2/n)
December 3, 2024 at 10:13 AM
With this broader motivation and in collaboration with Jean Baum's group, we brought to bear a number of computational and experimental biophysical tools (including cool Atomic Force Microscopy in Liquids!) to figure out how HtrA1 inhibits the aggregation and prion-like spread of a-synuclein. (2/n)